Neuroimaging and Neurostimulation: Going inside the black box Benzi M. Kluger M.D., M.S. Director, Movement Disorders Center Associate Professor of Neurology & Psychiatry University of Colorado
OUTLINE I. What is neuroimaging and neurostimulation? II. Brief history of neuroimaging and neurostimulation in Parkinson s? III. Why is this important? IV. What s in the research pipeline? V. What else is happening at the University of Colorado?
The Black Box
I. What is neuroimaging and neurostimulation?
Neuroimaging includes the use of various techniques to either directly or indirectly image the structure, function/pharmacology of the nervous system.
Neuroimaging What can we see inside the head? Structure Molecules Blood Flow Metabolic/Chemicals Activity Electrical Activity
Neuroimaging Computed Tomography (CT) Scan Positron Emission Tomography (PET) and Single photon emission computed tomography (SPECT) Scans (e.g. DAT Scan) Magnetic resonance imaging (MRI) Megnetoencephalography (MEG) and electroencephalography (EEG) Near Infrared spectroscopy (NIRS)
CT, PET and SPECT
DAT Scan
MRI
MEG/EEG
NIRS
Neurostimulation is a therapeutic activation of part of the nervous system using various techniques.
Neurostimulation Deep Brain Stimulation (DBS) Transcranial Magnetic Stimulation (TMS) Transcranial direct current stimulation (tdcs) Gene Therapy Cell Transplantation/Stem Cells (Ultrasound)
DBS
TMS
tdcs
Gene Therapy
Stem Cells
IIa. Brief History of Neuroimaging
History of Neuroimaging
Neuroimaging and Parkinson s There is no brain scan that can diagnose PD There is nothing that can be seen on an MRI DAT scan can assist in detecting a loss of dopamine neurons PET scans have found patterns of brain activity associated with both motor and nonmotor symptoms MRI scans have found changes in both grey matter and white matter
IIb. Brief History of Neurostimulation
History of Neurostimulation
History of Neurostimulation & PD Surgery in PD has a long history First use of DBS for tremor was in 1987 DBS rapidly became the surgical treatment of choice with targets in STN, GPI and thalamus PD is most widely used indication for DBS with over 100,000 implanted patients
III. Why is this important?
Neuroimaging: Mechanism
Neuroimaging: Biomarker A biomarker, or biological marker, generally refers to a measurable indicator of some biological state or condition Diagnostic Predictive Monitor Disease progression
IV. What s in the research pipeline?
Optogenetics
Biomarkers Imaging alpha-synuclein Connectivity Structural Functional
7 Tesla MRI
Deep Brain Stimulation Paramedian Pontine Nucleus (PPN) Stimulation for depression and dementia Neuroprotection? Smarter stimulators
Gene Therapy and Stem Cells All trials have been negative to date Dopamine replacement Neurotransmitter replacement Growth factors
Transcranial Magnetic Stimulation
Transcranial Direct Current Stimulation
V. Research at the University of Colorado
Getting Patients Involved Parkinson s Advocates in Research (PAIR) Grant Patient Centered Outcomes Research Institute (PCORI)
Marijuana Used by 5-10% of our patients Most helpful for non-motor symptoms New Grant from state of Colorado on CBD for tremor Also looking at memory and driving
Complementary and Alternative Medicine Acupuncture Massage Yoga Meditation
Exercise Different forms of exercise have different benefits SPARX study is looking into the question of what is the right dose Neuroprotective?
Neuroimaging fmri and PD phenotypes MEG and cognitive symptoms MRS and cognitive symptoms MEG and the benefits of rhythm on movement
Nonmotor Symptoms Palliative Care Fatigue Cognitive Impairment TMS treatment
Genetics PROGENI study More on the way
Neuroprotection Curt Freed and phenylbutyrate Margaret Schenkman and Exercise Katherine James and pesticides CoQ10 Creatine
Medications Long acting amantadine Botox for drooling Low dose azilect/mirapex